The specific protease, collagenase, holds a key role in the degradation of the extracellular matrix. This enzyme has been purified and characterized from culture medium of both normal (1,2,3) and abnormal (4,5) (recessive dystrophic epidermolysis bullosa) human skin fibroblasts. Secreted as a set of two closely related zymogens, collagenase can be activated by several mechanisms including autoactivation, trypsin, organomercurials, chaotropic ions, and naturally occurring tissue activators. The action of each of these agents will be characterized both kinetically and by employing amino acid sequence analysis. Monoclonal antibodies specific for the zymogen and trypsin activated forms of both normal and abnormal collagenase will be produced both for comparative biochemical studies as well as to help establish, by immunofluorescence, the molecular form of human skin collagenase as it exists in vivo. The information gained from these studies will more precisely define the significant events of connective tissue degradation and will serve to elucidate abnormalities relevant to diseases which produce alterations in the collagen matrix such as peidermolysis bullosa (6), rheumatoid arthritis (7), and certain connective tissue tumors (8).